Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder

Background: Functional brain imaging studies in unipolar lar and secondary depression have generally found decreased prefrontal cortical activity, but in bipolar disorders findings have been more variable. Methods: Forty-three medication-free, treatment-resistant, predominantly ra pid-cycling bipolar disorder patients and 43 age- and gender-matched health y control subjects had cerebral glucose metabolism assessed using positron emission tomography and fluorine-18-deoxyglucose. Results: Depressed bipolar disorder patients compared to control subjects h ad decreased global, absolute prefrontal and anterior paralimbic cortical, and increased normalized subcortical (ventral striatum, thalamus, right amy gdala) metabolism. Degree of depression correlated negatively with absolute prefrontal and paralimbic cortical, and positively with normalized anterio r paralimbic subcortical metabolism, Increased normalized cerebello-posteri or cortical metabolism,vas seen in all patient subgroups compared to contro l subjects, independent of mood state, disorder subtype, or cycle frequency . Conclusions: In bipolar depression, we observed a pattern of prefrontal hyp ometabolism, consistent with observations in primary unipolar and secondary depression, suggesting this is part of a common neural substrate for depre ssion independent of etiology, In contrast, the cerebello-posterior cortica l normalized hypermetabolism seen in all bipolar subgroups (including euthy mic) suggests a possible congenital or acquired trait abnormality. The degr ee to which these findings in treatment-resistant, predorninantly rapid-cyc ling patients pertain to community samples remains to be established. (C) 2 001 Society of Biological Psychiatry.